Preventing inherited diseases

New medical procedures are coming under review that could stop the transmission of incurable diseases from mother to child, but could result in crossing a line into irreversible genetic alterations

By Donna Dickenson

Illustration: Mountain People

The UK’s Human Fertilization and Embryology Authority (HFEA) has launched a public consultation to gauge attitudes toward controversial new medical procedures aimed at preventing the transmission of incurable diseases that result from mutations of cell structures called mitochondria. Supporters of such research are framing criticism of it as opposition to saving children’s lives and an impediment to scientific development. However, this view neglects a crucial factor in the debate: the techniques being developed involve permanent genetic alterations passed on to future generations.

The mitochondria are the energy-producing “batteries” of the cell, containing the only DNA outside of the cell nucleus — 37 genes, or roughly 0.2 percent of a person’s genetic makeup. Given that these genes are contained in the egg, and thus are inherited only from the mother, the new techniques aim to replace the mother’s mutated mitochondria with that of a healthy female donor of eggs without the mutation. This results in embryos that contain genetic material from three people — the child’s father and mother, plus the egg donor.

So the real question is how the public feels about crossing the line between medical treatments for existing people and irreversible genetic alterations that would be passed on to future generations through genetic modification of the human germline (the sequence of germ cells, such as sperm and eggs, containing genetic material that a child may inherit).

MUTATIONS

Despite the good intentions behind mitochondrial research, international concern about the implications of breaching this barrier is mounting. Indeed, not only do most scientists and governments worldwide consider human germline genetic modification unacceptable; it is expressly prohibited in more than 40 countries, including the UK. As a result, experts in the US, Canada, Germany, Israel and elsewhere have responded critically to the prospect of Britain unilaterally undermining the consensus that prohibits such techniques.

Mitochondrial mutations can have serious consequences, including epilepsy, liver failure, diabetes and cardiomyopathy. However, while the number of people affected by such mutations is estimated to be between one in 200 and one in 400, mutations do not translate to serious diseases in most cases. Because the harmful changes are often only present in low levels, and because a single cell can contain both mutated and normal mitochondria, it is widely believed that only one person in 5,000 — or even one in 10,000 — will be affected by mitochondrial disease.

Despite this relatively low frequency, the Wellcome Trust (an organization dedicated to improving human and animal health) recently donated ￡4 million (US$6.5 million) to scientists at the University of Newcastle to establish a center for mitochondrial research. In a 2010 paper, the scientists reported some early success with a technique involving the use of human zygotes (single-cell embryos) that had been engineered to contain only healthy mitochondria. However, they managed to develop only 8 percent of the zygotes to a slightly later stage.

Nevertheless, last year a coalition of scientists and funders submitted a letter to former UK secretary of state for health Andrew Lansley requesting regulation revision, in order to permit the new techniques’ use in clinical treatment “once sufficient pre-clinical evidence [was] established.” The influential groups backing the coalition — including the UK Academy of Medical Sciences, the Medical Research Council and the Wellcome Trust — claimed that “translating research into treatment [looked] achievable in the near future.”